A number of misconceptions regarding biological olfaction are widely held, including by many experts in the field. These misconceptions have adversely impacted the design of electronic olfactors (commonly known as electronic noses or E-noses).
First Misconception: By determining what a volatile mixture is made of (chemical identity and accurate relative concentrations of odorants), one can predict what the mixture smells of and vice versa. This is often incorrect.
Correct: Actually, a single-molecule odorant (or set of odorants) can confer different scents (a) at different concentrations, (b) in different mixtures, (c) at different ambient humidity, temperature, or pressure, or (d) at different times post first exposure.
Second Misconception: Humans use the same “olfactory handle” when identifying odorants in different environments—analogous to specific peaks in gas chromatography mass spectrometry (“GC/MS”). This is often incorrect.
Correct: Actually, olfactory recognition handle(s) can change to dynamically adapt to recognition task requirements (and general training in one environment can carry on to a completely different environment with the specific “handle”). Sensory input is constantly being compared to memory of training experience and “attention” is focused “retroactively”. This means different features of a neural activation pattern become salient in different backgrounds. Many recognizable scents (e.g. coffee, “olfactory white”) do not have a well-defined molecular blueprint.
Third Misconception: The perceived scent of a combination of odorants is equal to the weighted sum of the scents of the individual odorants. This is often incorrect.
Correct: Actually, the scent of a combination of odorants can be quite different than the weighted sum of the scents of the individual odorants.
The above misconceptions form the basis of a conventional explanation of biological olfaction. Under this conventional explanation, biological olfaction consists of analytical measurement followed by pattern recognition, as follows: first steps involve molecule-identifying olfactory receptor (OR) binding events that cause conformational changes depolarizing the membrane of olfactory receptor neurons (ORNs) in the olfactory epithelium followed by local (or olfactory bulb or possibly higher brain) pattern recognition culminating in a reliably reproducible scent experience.
However, this conventional explanation describes only part of the mechanism and is only partially correct. It is incorrect to the extent it fails to recognize the importance of odorant conformation, possible mixture chemistries, agonist/antagonist effects, allosteric modulation of receptors, and complex feedback and modulation effects such as habituation, attention, generalization, etc. More importantly, this conventional explanation fails to recognize that: (1) the same single-molecule odorant can confer different scents at different concentrations, in different mixtures, at different ambient humidity, temperature, or pressure, or at different times post first exposure; and (2) the scent of a combination of odorants cannot, in many cases, be accurately predicted from the chemical identity and relative concentrations of the odorants in the combination.
Part of the reason why these misconceptions persist is because biological olfaction often appears analytical. These are many cases when the presence of a single molecule in a broad range of concentrations and against many backgrounds unambiguously dominates the odor character. Examples are vanillin, ammonia, hydrogen sulfide (rotten eggs), and skatole (feces).
However, in many cases, a scent is not defined by one unambiguously responsible molecule. For example, the scents of coffee, wine and roasted food are each formed by a combination of hundreds or thousands of odorants.
“Olfactory white” is a striking example of how the scent of a combination of odorants (a) is not necessarily defined by a single odorant in the combination, and (b) can be very different than weighted sum of the scents of the individual odorants that form the combination. Tali Weiss et al.; Perceptual convergence of multi-component mixtures in olfaction implies an olfactory white; Proceedings of the National Academy of Science of the United States of America, published online before print, PNAS, Nov. 19, 2012, doi:10.1073/pnas.1208110109 (“Olfactory White Paper”).
In the recent Olfactory White Paper, the authors report that different mixtures of approximately 30 odorants tend to smell alike to human subjects, even though the different mixtures do not share all components in common. The different mixtures tend to converge to an olfactory white when there are at least 30 odorants in each mixture, and the odorants are non-overlapping, of equal intensity, and as a whole span olfactory space.
In the Olfactory White Paper, p. 19963, the authors observe that:                “Olfaction is . . . a synthetic rather than analytical sensory system. For example, humans are very poor at identifying components in a mixture, even when they are familiar with the components alone. Similarly, cortical patterns of neural activity induced by a mixture are unique, not a combination of neural activities induced by the mixtures' components . . . . In other words, the olfactory system treats odorant mixtures as unitary synthetic objects and not as an analytical combination of components . . . . ” (citations omitted)        
In biological allosteric modulation, the binding of a (partial) agonist, antagonist or modulator protein to a receptor protein in turn modulates the effect of the binding of a specific ligand to that receptor protein.